ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4269G>A (p.Leu1423=) (rs45438898)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000177761 SCV000169147 benign not specified 2013-05-03 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000163262 SCV000213790 likely benign Hereditary cancer-predisposing syndrome 2014-08-11 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000177761 SCV000229689 likely benign not specified 2014-08-15 criteria provided, single submitter clinical testing
Invitae RCV001084395 SCV000262304 benign Tuberous sclerosis 2 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000177761 SCV000305216 likely benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000042548 SCV000395649 benign Tuberous sclerosis syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Integrated Genetics/Laboratory Corporation of America RCV000590662 SCV000697469 benign not provided 2016-08-23 criteria provided, single submitter clinical testing Variant summary: The c.4269G>A (p.Leu1423=) in TSC2 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.0023 (305/99578 chrs tested), including 2 homozygous occurrences. This frequency exceeds the estimated maximum allele frequency for a pathogenic allele in this gene (0.0000068). The variant of interest has been cited as Benign/Likely Benign by multiple reputable databases/clinical laboratories. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000177761 SCV000711365 benign not specified 2017-09-22 criteria provided, single submitter clinical testing p.Leu1423Leu in exon 34 of TSC2: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.2% (737/265766) of chromosomes, including 4 homozygotes) and the highest allele frequency of 0 .5% in Ashkenazi Jewish by the Genome Aggregation Database (gnomAD, http://gnoma d.broadinstitute.org; dbSNP rs45438898)
Athena Diagnostics Inc RCV000590662 SCV001146285 benign not provided 2018-09-30 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000177761 SCV001157411 benign not specified 2019-01-30 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000042548 SCV000066342 not provided Tuberous sclerosis syndrome no assertion provided curation

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